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101.
Twenty-four-hour records of arterial pressure (AP), heart rate(HR), oral temperature (OT) and physical and mental performancewere obtained in air traffic controllers during morning (n=16),afternoon (n=17) and night (n=19) shifts. Data were analyzedby the cosinor method. The results obtained during the morningshift were as follows (mesor/amplitude/;acrophase): systolicAP (mm Hg)113.6/10.0/16:03 h; diastolic AP71.1/8.215:19h; mean AP85.6/8.8/15:41 h; HR (beats/min)77.5/8.9/16:00h; OT (dg C)36.71/0.21/15:49 h; right-hand grip strength(kg)49.8/2.0/17:43 h; left-hand grip strength46.1/2.0/16.08h; mental performance (calculations/min)14.9/1.1/16:39h. During the night shift either no change of the circadianacrophases (HR, right-hand grip strength) or acrophase delaysranging from about 2 h (systolic AP, OT, mental performance)up to 3 h (diastolic and mean AP, left-hand grip strength) wereobserved. Our data suggest that the shift system studied doesnot significantly alter the circadian rhythms, and does notinduce a desynchronization, particularly as concerns arterialpressure and oral temperature. 相似文献
102.
Brett Claire M. Washington Carla B. Ott Ronda J. Gutierrez Marcelo M. Giacomini Kathleen M. 《Pharmaceutical research》1993,10(3):423-426
The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na+-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na+-driven 3H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na+–uridine transport was determined. At a concentration of 100 µM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na+-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na+-uridine uptake with a K
i of 26.4 µM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na+–nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The K
i of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside. 相似文献
103.
P.H. Andersen H. Vestergaard S. Lund P. Vedel S. Junker B.B. Kahn O. Pedersen 《Diabetic medicine》1993,10(8):699-706
Studies in normal man and rodents have demonstrated that the expression of the dominant glucose transporter in skeletal muscle, GLUT4, is regulated by insulin at supraphysiological circulating levels. The present study was designed to determine whether intensified insulin replacement therapy for 24 h given to patients with Type 1 diabetes in poor metabolic control was associated with an adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle. Nine Type 1 diabetic patients with a mean HbA1c of 10.3% were included in the protocol. After intensified treatment with soluble insulin for 24 h the fasting plasma glucose concentration decreased from 20.8 ± 2.3 (SD) to 8.7 ± 2.3 mmol 1?1 whereas the fasting serum insulin level increased from 0.06 ± 0.02 to 0.17 ± 0.09 nmol 1?1 However, despite a 2.8-fold increase in serum insulin levels and more than a halving of the plasma glucose concentration for at least 15 h no significant alterations occurred in the amount of GLUT4 protein (0.138 ± 0.056, poor control vs 0.113 ± 0.026 arb. units, improved control, p = 0.16) or GLUT4 mRNA (96432 ± 44985, poor control vs 81395 ± 25461 arb. units, improved control, p = 0.54). These results suggest, that in spite of evidence that high insulin levels affect GLUT4 expression in muscle, changes in serum insulin within the physiological range do not play a major role in the short-term regulation of GLUT4 expression in Type 1 diabetic patients. 相似文献
104.
Patrick Goethals Manuella Coene Guido Slegers Philippe Agon Joris Deman Karel Schelstraete 《European journal of nuclear medicine and molecular imaging》1988,14(3):152-154
A method for producing carrier free 66Ga (T1/2:9.4h; +) by 4He bombardment of natural copper targets is presented. 66Ga is formed by means of the 63Cu (4He, n) 66Ga reaction. Production yields are given in the 17.5 to 8 MeV 4He energy range. Chemical purification of 66Ga from the copper target is described. The only radionuclidic impurity found in the final product was 67Ga. Albumin colloids from commercially available kits designed for use with 99mTc could easily be labeled with 66Ga and employed for studies of the lymphatic system by positron emission tomography. 相似文献
105.
杜康宁 《中国脊柱脊髓杂志》1988,(2)
本文阐述用“包络—轨迹”法修正齿形的齿形链在传动中齿形干涉区的确定,单向传动中增强齿强度的途径,双向传动中避免齿形干涉的设计方法。最后讨论了链节的受力分析,链传动结构容纳节距伸长能力问题。 相似文献
106.
Smith Philip Mirabelli Christopher Fondacaro Joseph Ryan Frederick Dent John 《Pharmaceutical research》1988,5(9):598-603
We have employed an in vitro system to study transport and metabolism of organic molecules by gastrointestinal tissues. Such a system would aid in the evaluation of the potential for oral delivery of organic molecules. Transport and metabolism of 5-fluorouracil (5-FU) were studied using rabbit intestinal preparations. Unidirectional fluxes and metabolism were measured in vitro in Ussing chambers under short-circuit conditions. Results from these studies reveal that in ileum, proximal, and distal colon, steady-state fluxes of 5-FU (10 µM added to both bathing solutions) are established after 30 min and remain constant for at least 110 min. Transport of 5-FU under sink conditions with 10 µM 5-FU present in the mucosal or serosal bathing solution alone demonstrated similar rates of transport as under nonsink conditions. The concentration dependence of 5-FU fluxes indicates that the mucosal (m)-to-serosal (s) flux is composed of both a saturable and a linear component over the range of 1–100 µM in the ileum, whereas the s-to-m flux in the ileum and both fluxes in the colon are linear functions of concentration. Over the concentration range employed and the time course of these studies, 5-FU had no effect on the electrical properties of the ileum or colon. In the ileum, the m-to-s but not the s-to-m flux of 5-FU was reduced by (1) serosal ouabain (0.1 mM); (2) reduction of the bathing solution Na concentration; and (3) addition of uracil, thy mine, thymidine, uridine, 2-deoxyuridine, or uridine-5-monophosphate. These results indicate that 5-FU absorption in the ileum occurs by a Na-dependent mechanism that is inhibited by uracil and structurally related compounds. In distal colon, no evidence for an active transport mechanism was obtained. High-performance liquid chromatography (HPLC) analysis reveals that both ileum and distal colon metabolize 5-FU to more polar compounds. Metabolism in ileum is quantitatively greater than in distal colon. Metabolites are found predominantly on the side to which transport has occurred, suggesting that metabolism occurs concomitantly with transport. Since the intestinal cells metabolize 5-FU to more polar compounds and active absorption is inhibited in a competitive manner by related compounds, these results may provide an explanation for the variable oral activity reported for 5-FU. 相似文献
107.
Willy Van Driessche David Erlij Isabelle Aelvoet 《Pflügers Archiv : European journal of physiology》1990,417(3):342-348
The role of Ca2+ in the regulation of antidiuretic hormone(ADH)-induced water permeability of the apical membrane of the toad urinary bladder was examined. The effects of modifying Ca2+ entry through the apical membrane of toad urinary bladders on the hydroosmotic water flow H2O) and short circuit current (I
sc) were measured. In most experiments the bladders were treated with small amounts of Ag+ (10–7 mol/l) on the apical side. This treatment was used because previous experiments indicate that it markedly increases alkali-earth cation fluxes through an amiloride-insensitive cation channel in the apical membrane of the urinary bladder. Moreover, when Ca2+ is the major cation in the apical solution of these Ag+-treated bladders, I
sc is mostly due to Ca2+ entry through the apical membrane. Ag+ increased I
sc and simultaneously inhibited H2O in bladders perfused with Ca2+ solutions on the apical side. Addition of La3+ to the apical solution reversed the stimulation of I
sc and the inhibition of H2O produced by Ag+. When bladders were perfused with Ca2+-free solutions on the apical side, addition of Ag+ did not inhibit H2O while the stimulation of cation movements through the amiloride-insensitive cation channel persisted. In bladders perfused with apical Ca2+ solutions and treated with chlorophenyl thio-cyclic adenosine monophosphate (ClPheS-cAMP) the addition of Ag+ did not inhibit H2O while it still increased I
sc. Finally, addition of Ca2+ to the apical solution of bladders not treated with Ag+ reduced H2O. These results taken together with other findings in the literature suggest: (1) Ca2+ entry through the Ag+-treated amiloride-insensitive cation channel of the apical membrane inhibits H2O; (2) the effects of Ca2+ entry are at a regulatory site that precedes the interaction of cAMP with the water channels; (3) it is also possible that Ca2+ entry through the unmodified amiloride-insensitive cation channel may have some inhibitory effect on H2O. 相似文献
108.
Previous work in our laboratory has shown that neural trauma results in a disparity between oxidative and glycolytic rates. In non-neural tissue, glycolysis and oxidative phosphorylation have been shown to work independently of one another, a phenomenon known as "energy compartmentalization". We believe that functional compartmentalization of energy production may also occur in the brain with glycolysis providing energy for membrane bound ionic pumps. Spreading depression, induced in rodent brain by topical KCl application, results in K+ shifts. The restoration of K+ gradients is accomplished by energy dependent Na(+)-K+ pumps. If these pumps depend upon glycolysis, blocking glycolysis should prevent reconstitution of normal [K+]e levels. The present series of experiments were designed to suggest that energy compartmentalization may also exist in brain, and that glycolytic energy production is preferentially used by Na(+)-K+ pumps to maintain normal ionic homeostasis by observing the dynamics of spreading depression induced K+ shifts before and after glycolytic blockade. Spreading depression was associated with increased K+ (48.6 +/- 16.6 mM over control) that normalized within 2.9 +/- 0.3 minutes. Following superfusion with a glycolytic blocking agent, spreading depression produced similar increases in [K+]e (40.6 +/- 12.0 mM over control) but time for reconstitution of the normal [K+]e was 400% longer than controls (2.9 +/- 0.3 to 14.9 +/- 2.1 minutes, P less than 0.001). Time required for recovery of EEG was identical pre- and post-blockade. We believe these data suggest that energy compartmentalization may exist in neural tissue and that glycolytic pathways of energy production are functionally tied to membrane Na(+)-K+ pumps.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
109.
A. Awad P. Govitrapong Y. Hama M. Hegazy M. Ebadi 《Journal of neural transmission (Vienna, Austria : 1996)》1989,76(2):129-144
Summary The high concentration of zinc in the bovine pineal gland prompted us to investigate the existence of a zinc-binding protein in this organ. In this study, we report that the subcellular distribution of zinc in the bovine pineal gland is nonuniform, with the crude nuclear, mitochondrial, microsomal, and supernatant fractions having 0.264±0.038, 0.160±0.019, 0.130±0.016, and 0.287±0.010 g zinc/mg protein, respectively. Furthermore, gel filtration studies using Sephadex G-75 and a 105,000 g supernatant fraction revealed two zinc binding protein peaks that bind 1.7 and 3.7 g Zn++/mg protein, respectively. Furthermore, purification of the protein peak with an elution volume (ve/vo) of 2.06 on anion exchange chromatography (DEAE-A 25) yielded a single protein peak which binds 10 g zinc/mg protein. The comparative high performance liquid Chromatographic (HPLC) profiles of the zinc-induced hepatic metallothionein isoform I (retention time=17.39 min) and of the bovine pineal metallothionein-like protein isoform I (retention time=17.49 min) are similar. Since zinc is a potent inhibitor of sulfhydryl-containing enzymes and receptor sites, we investigated the effects of zinc and found that it inhibited the binding of [3H]glutamate (IC 50=80 M) and of [3H]spiroperidol (IC 50=0.6 mM) to the pineal membranes. The results of these studies are interpreted to indicate that the bovine pineal gland possesses an active and dynamic zinc homeostatic mechanism, whose precise function(s) remain(s) to be delineated. 相似文献
110.
P. Lijnen R. Fagard J. Staessen T. Weiping E. Moerman A. Amery 《European journal of clinical pharmacology》1989,37(6):609-611
Summary The effect of cromakalim, a K+-channel activator, on the plasma renin-angiotensin-aldosterone system, catecholamines and -atrial natriuretic peptide, and on the intraerythrocyte concentration and transmembrane fluxes of Na+ and K+ has been investigated in 18 normal male subjects, in a double-blind parallel study. After a run-in period on placebo for 1 week, the subjects were treated either with placebo (n=6) or cromakalim (n=12) for 1 week.Plasma renin activity was significantly increased during cromakalim. No effect of cromakalim on plasma angiotensin II, aldosterone, adrenaline, noradrenaline and -atrial natriuretic peptide was demonstrated. The intra-erythrocyte K+ concentration was decreased during cromakalim administration and Ca2+-dependent K+-channels in red blood cells were increased. 相似文献